MOA of Minoxidil
- K+ channel regulator
- opens potassium channels and stabilizes the membrane
- cells become hyperpolarized -> relax -> vasodilate
- dilates arterioles but not veins
adverse effect of Minoxidil
hypertrichosis: excessive hair growth
MOA of Fenoldopam
- specific agonist on D1 receptors
- causes relaxation of arteriolar smooth muscle
indications of Fenoldopam ? route of administration
- used for emergency hypertensive situations
- IV; half life 5 min
What are Dihydropyridines
- calcium channel blockers
- Nifedipine, Nimodipine; (-dipines)
MOA of calcium channel blockers
- bind to L-type channels in the myocardium and vascular smooth muscle which causes channels to close
- get long lasting relaxation of vascular smooth muscles
- decreased cardiac contractility, automaticity, and conduction
which systems are effected by calcium channel blockers
- will relax all smooth muscles
- vascular smooth muscle is the most sensitive, but bronchiolar, GI, and uterine are also relaxed
- arterioles are more sensitive than veins
what are the major cardiac effects of CCBs
- negative inotropic effect due to decreased contractility
- reduced impulse generation in SA node
- slowed AV node conduction
Diltiazem and Verapamil fall under what drug class
calcium channel blockers
Differentiate between Nifedipine, Verapamil, and Diltiazem
- Nifedipine: strongest vasodilator (inc HR due to reflex tachycardia)
- Verapamil: strongest cardiac effects (dec HR)
- Diltiazem: in between
CCB
- route of administration
- excretion
- half-life
- oral
- renal excretion
- half life 3-5 hrs
which CCB is the most likely to produce reflex tachycardia
- Nifedipine
- highest vasodilation -> marked hypotension -> reflex tachycardia
which CCB is the most likley to cause depressed SA and AV node function
verapamil
adverse effect of dihydropyridines
- cause the most vascular side effects: HA, flushing, dizziness, peripheral edema
- gingival hyperplasia
what is the most common side effect of verapamil
constipation
Dihydropyridines should be used cautiously in patients with what condition
hypertensive patients with CHF
Verapamil and Diltiazem are contraindicated in patients with
- SA or AV node abnormalities
- CHF
explain RAAS
- angiotensinogen is made by liver, freely flowing i nblood
- rate limiting step: release of renin
- renin converts angiotensinogen -> angiotensin I
- angiotensin I comes into contact with ACE in the lungs and it is converted to Angiotensin II
- Ang II -> vasoconstriction and aldosterone secretion
what is another function of ACE besides converted Ang I to Ang II
ACE is responsible for bradykinin degradation; bradykinin effects Prostaglandins and causes vasodilation so ACE causes vasoconstriction
Effect os ACE-inhibitors
- drop BP
- reduce vasoconstriction by ang II
- reduce release of aldosterone
- cause vasodilation through bradykinin
- does not not reflex sympathetic activation (tachycardia) because of baroreceptor resetting
ACE-I are most effective in what patient popuations
white, young
ACE-I are the DOC for treatment of hypertensives with what conditions
- DM
- **diabetic nephropathy
- CKD
- left ventricular hypertrophy (CHF)
why are ACE-I often combined with diuretics
- enhance antihypertensive efficacy of diuretic drugs
- inhibit aldosterone so natriuresis is unopposed
- balance adverse effects on potassium of diuretics
adverse effects of ACE-I
- will cause severe hypotenstion in hypovolemic patients
- hyperkalemia
- cough
- angioedema
- acute renal failure in patients with bilat renal artery stenosis
